Could treating EDS reduce Alzheimer's risk?

Action Points

Note that this longitudinal study found that excessive sleepiness at baseline was associated with a greater accumulation of amyloid protein among elderly patients without dementia.

Be aware that the link between these processes is unclear, but sleep may provide an opportunity for clearance of soluble amyloid.

Excessive daytime sleepiness in older people without dementia was associated with increased β-amyloid accumulation over time, in the first longitudinal study to examine sleep disturbance and the Alzheimer's disease biomarker.

Previous cross-sectional research has linked poor sleep and dementia in elderly populations, and earlier longitudinal studies have shown an association between excessive daytime sleepiness and dementia risk.

But the novel finding of increased β-amyloid accumulation in patients self-reporting excessive daytime sleepiness at baseline provides new evidence of the direction of the association, Prashanthi Vemuri, PhD, of the Mayo Clinic in Rochester, MN, told MedPage Today.

She said the findings of her team, published in JAMA Neurology, suggest that older people with excessive daytime sleepiness may be more vulnerable to the pathologic changes that lead to Alzheimer disease (AD).

The researchers noted that sleep is believed to be a key factor in regional β-amyloid (Aβ) clearance, leading to the hypothesis about disturbed sleep: "Because sleep has been proposed to participate in the clearance of soluble Aβ, disturbed sleep has been suggested to contribute to Aβ accumulation. Conversely, Aβ accumulation appears to further disrupt sleep or the sleep-wake cycle in animal models, which is corroborated by correlational studies in humans."

Vemuri and colleagues investigated whether excessive daytime sleepiness at baseline was associated with longitudinal increases in regional Aβ accumulation in a group of 283 elderly (age 70 or older) participants without dementia.

All completed surveys assessing sleepiness at baseline, and all had at least two consecutive Pittsburgh compound B positron emission tomography (PiB-PET) scans between January 1, 2009 and July 31, 2016.

Excessive daytime sleepiness was defined as an Epworth Sleepiness Scale score of at least 10. The difference in Aβ levels between the two consecutive scans (ΔPiB) in Aβ-susceptible regions (prefrontal, anterior cingulate, posterior cingulate-precuneus, and parietal) was determined.

"It remains unclear whether excessive daytime sleepiness is a result of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. However, participants with excessive daytime sleepiness were more vulnerable to AD pathologic processes."

Vemuri noted that future longitudinal studies should follow younger patients, starting in their 50s, for longer periods -- "This is when we begin to see changes in amyloid."

Writing in an accompanying editorial, Joseph Winer, MA, and Bryce Mander, PhD, of the University of California's Berkeley and Irvine campuses, respectively, said that an important implication of the findings is that "self-report of subjective sleepiness may serve as a simple but effective scientific and clinical tool in assessing AD risk."

They urged caution, however, in interpreting the findings, given that self-reported sleep measurement is an important study limitation, and while the mechanism linking poor sleep to β-amyloid accumulation is not known, there are several possibilities: "First, sleep fragmentation and disruption of non-REM sleep contribute to daytime sleepiness, are common in aging, and have been linked to AB cross-sectionally. Second, obstructive sleep apnea has been linked to Aβ accumulation and is an established risk factor for cognitive decline ... Third, other disorders of shortened or disturbed sleep, such as insomnia, may have driven the observed differences."

Winer and Mander suggested that future studies should include other biomarkers of AD progression, such as tau deposition, cortical atrophy, and cardiovascular changes.

Funding for the research was provided by the National Institutes of Health, the Gerald and Henrietta Rauenhorst Foundation, the Mayo Foundation, and others.

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